Physical mobility, physical activity, and obesity among elderly: findings from a large population-based Swedish survey.

OBJECTIVE: To examine how physical activity and physical mobility are related to obesity in the elderly. STUDY DESIGN: A cross-sectional study of 2558 men and women aged 65 years and older who participated in a population survey in 2012 was conducted in mid-Sweden with an overall response rate of 67%. METHODS: Obesity (body mass index ≥30 kg/m2) was based on self-reported weight and height, and physical activity and physical mobility on questionnaire data. Chi-squared test and multiple logistic regressions were used as statistical analyses. RESULTS: The overall prevalence of obesity was 19% in women and 15% in men and decreased after the age of 75 years. A strong association between both physical activity and obesity, and physical mobility and obesity was found. The odds for obesity were higher for impaired physical mobility (odds ratio [OR] 2.83, 95% confidence interval [CI] 2.14-3.75) than for physical inactivity (OR 1.63, 95% CI 1.28-2.08) when adjusted for gender, age, socio-economic status and fruit and vegetable intake. However, physical activity was associated with obesity only among elderly with physical mobility but not among those with impaired physical mobility. CONCLUSION: It is important to focus on making it easier for elderly with physical mobility to become or stay physically active, whereas elderly with impaired physical mobility have a higher prevalence of obesity irrespective of physical activity.

Role of autonomic nervous system and the cough reflex in the increased responsiveness of airways in patients with obstructive airway disease.

Inhalation of aerosols of citric acid, histamine phosphate, or carbon dust, or air cooled to - 20 degrees C or rapid respiratory maneuvers (inspiration or expiration) results in an increase in airway resistance in some patients with asthma or bronchitis. It has been shown previously in animals that stimulation of cough receptors results in bronchoconstriction through efferent cholinergic pathways. In the patients studied, the administration of atropine sulfate, which would block such pathways, abolished the bronchoconstrictor effects of all the stimuli except large doses of histamine, which may exert a direct effect on airway smooth muscle. These data suggest that sensitized cough receptors may be involved in triggering reflex airway constriction in such patients.

Treatment and outcome of 2904 CML patients from the EUTOS population-based registry.

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia.

In patients with chronic myeloid leukemia (CML), first-line imatinib treatment leads to 8-year overall survival (OS) probabilities above 80%. Many patients die of reasons unrelated to CML. This work tackled the reassessment of prognosis under particular consideration of the probabilities of dying of CML. Analyses were based on 2290 patients with chronic phase CML treated with imatinib in six clinical trials. 'Death due to CML' was defined by death after disease progression. At 8 years, OS was 89%. Of 208 deceased patients, 44% died of CML. Higher age, more peripheral blasts, bigger spleen and low platelet counts were significantly associated with increased probabilities of dying of CML and determined a new long-term survival score with three prognostic groups. Compared with the low-risk group, the patients of the intermediate- and the high-risk group had significantly higher probabilities of dying of CML. The score was successfully validated in an independent sample of 1120 patients. In both samples, the new score differentiated probabilities of dying of CML better than the Sokal, Euro and the European Treatment and Outcome Study (EUTOS) score. The new score identified 61% low-risk patients with excellent long-term outcome and 12% high-risk patients. The new score supports the prospective assessment of long-term antileukemic efficacy and risk-adapted treatment.

Interactions between cladribine (2-chlorodeoxyadenosine) and standard antileukemic drugs in primary cultures of human tumor cells from patients with acute myelocytic leukemia.

The semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein in microtiter plates, was used for in vitro evaluation of Cladribine (2-chlorodeoxyadenosine, CdA) interactions with five standard antileukemic drugs: amsacrine (Am), etoposide (VP16), daunorubicin (Dnr), cytosine arabinoside (AraC), and mitoxantrone (Mit). Samples from 31 patients with acute myelocytic leukemia (AML) were tested with continuous drug exposure. A large heterogeneity with respect to cell kill was observed for all combinations tested. An additive model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) only for CdA+AraC. When the frequency of additive and synergistic interactions were calculated according to the multiplicative concept for drug interactions, the highest frequencies were observed for CdA+AraC and CdA+Dnr. This interaction pattern was confirmed by isobologram analysis. Cross-resistance analysis revealed high correlations between CdA and AraC whereas the correlations were weaker between CdA and the other drugs. The highest frequency of synergistic interactions was obtained for AraC+CdA, despite their cross-resistance. Of the non-cross-resistant drugs tested, Dnr appears to be the most effective adjunct to CdA in terms of interactions at the cellular level.

Regeneration of functional and activated NK and T sub-subset cells in the marrow and blood after autologous bone marrow transplantation: a prospective phenotypic study with 2/3-color FACS analysis.

The phenotypic reconstitution of lymphoid cells in the bone marrow and peripheral blood was examined prospectively in 27 patients who underwent autologous bone marrow transplantation (ABMT) for leukemia/lymphoma. Patterns of activation within NK and T cell subsets as well as T sub-subsets were studied with monoclonal antibodies in two- and three-color FACS analysis. NK-like cells (CD16+) were found to be increased in the peripheral blood and bone marrow after ABMT. The expression of two activation markers, 4F2 and HLA-DR, was sustainedly increased within this subset. High numbers of CD4+ and CD8+ T cells carrying surface HLA-DR were found early after ABMT both in blood and marrow. The T suppressor inducer cell sub-subset (CD45R+ CD4+) was severely depressed in both the blood and marrow 6-9 months post-ABMT. Using three-color FACS analysis, half of this T sub-subset was shown to express HLA-DR+. The levels of T suppressor effector-like cells (CD11+ CD8+) remained within the normal range in both peripheral blood and bone marrow during follow-up. The HLA-DR expression was elevated and equally distributed between the CD11- CD8+ and CD11+ CD8+ sub-subset cells. There was no major impact of marrow T cell purging or CMV carrier status on the phenotypic NK/T cell reconstitution. The present results provide an immune phenotypic basis for the suggested generation of anti-leukemic NK-like and T suppressor-like activity after ABMT.

Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia.

We have analyzed the M-bcr breakpoint position in 133 Philadelphia-positive chronic myeloid leukemia patients and correlated the findings with clinical, hematologic, and cytogenetic data. We also investigated the splicing pattern of the BCR-ABL mRNA in 30 patients, using reverse transcriptase PCR. No statistically significant differences were found between breakpoint position within M-bcr and clinical parameters at diagnosis, the karyotypic evolution pattern, or the leukemic phenotype during blast crisis. Furthermore, the breakpoint position within M-bcr did not correlate with the duration of chronic phase or survival time. When the splicing pattern of the BCR-ABL mRNA was compared with the results of the genomic breakpoint mapping, it was found that approximately 60% (8/14) of the patients with a 5' break expressed b2a2 fusion mRNA, whereas all patients (10/10) with a 3' break expressed b3a2 BCR-ABL mRNA.

Autologous bone marrow transplantation in acute lymphoblastic leukemia--preclinical immunologic studies.

Immunologic aspects of autologous bone marrow transplantation (ABMT), immunodiagnosis, patient monitoring, and the purging of bone marrow have been studied in individual patients. It was demonstrated that the most sensitive method for detecting lymphoid cells which show the phenotypes of ALLs of B or T lineage was double immunofluorescence staining for nuclear terminal transferase (TdT) and B or T lineage antigens. With the help of these sensitive tests in the presence of rabbit complement (C'), MAbs CD10 (RFAL3 of IgM class), CD19 (SB4 of IgM class), and their cocktail were capable of eliminating greater than 3 log blast cells of B lineage ALL in 84%, 75.5%, and 90% of cases, respectively. The same reagents lysed 26.8%, 0%, and 45% of blasts in the presence of human C'. CD7 (RFT2, IgG2) eliminated greater than 3 log T-ALL blast cells in 73% of cases. The proliferative fractions of leukemic blasts were also TdT+ and sensitive to lysis with MAb and C'. On the basis of these observations MABs were selected for purging in 36 patients undergoing ABMT in first remission (10 patients considered to be at a high risk of relapse), second and third remissions (23 and 2 patients), and without entering into remission (1 patient). The efficacy of eliminating the MAb-reactive cells from the bone marrow inoculum was also documented in five patients. By the use of sensitive immunologic assay (TdT/cytoplasmic CD3 double staining) in patients with T-ALL, no residual leukemia (less than 10(-4] could be detected at the time of transplantation. Following an observation period of 5-34 months, 24 of the 36 patients are alive and well with no procedure-related mortality.

Autologous bone marrow transplantation with monoclonal antibody purged marrow for high risk acute lymphoblastic leukemia.

Fifty-four patients with acute lymphoblastic leukemia (ALL: 1 relapse, 21 high risk first complete remission (CR 1), 29 second CR (CR 2), and 3 third CR (CR 3) were treated by autologous bone marrow transplantation at three centers. Before storage, the marrows were purged ex vivo with appropriate MAbs RFAL3 (CD10), SB4 (CD19), and RFT2 (CD7), with rabbit serum as the source of complement. All patients received total body irradiation either 750 cGy (middose 15 cGy/min) as a single fraction or 6 x 200 cGy over 3 days (midline dose 16 cGy/min) with lung shielding from 1,100 cGy. The patients who received 750 cGy also received cyclophosphamide or the same drug combined with ara-C or prednisone, teniposide, vincristine, ara-C, and dauno-rubicin. Patients receiving 200 cGy x 6 also received either cyclophosphamide, melphalan, or ara-C and cyclophosphamide. Three patients died of post transplantation complications (interstitial pneumonia, hepatitis B liver necrosis, or encephalitis). This gives a procedure related mortality of 5%. Nonfatal complications were 10 cases of septicemia, 4 interstitial pneumonia, 2 interstitial nephritis, 1 veno-occlusive disease (VOD), and 1 case of hemolytic uremic syndrome. The patient autografted in relapse died of relapse within 2 months. In CR 1 6 or 21 patients have had a relapse, and the actuarial leukemia free survival from CR is 65% (median follow-up 16 months). In CR 2-3 18 of 32 patients have relapsed, and the actuarial leukemia free survival is 31% (median follow-up 18.5 months) from CR. Twelve patients have achieved an inversion, (i.e., present CR longer than previous CR), with a further seven with the potential to achieve inversion. We conclude that ABMT in high risk ALL has a low procedure related mortality (5%), and there are few other complications. The in vitro purging with MAbs had no adverse effect on bone marrow reconstitution, but this study was not designed to demonstrate its antileukemic efficacy. The actuarial leukemia free survival time in the present study for patients with high risk CR 1 and the inversions in CF 2-3 are promising and indicate a potential beneficial effect of ABMT.

The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries.

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

Serum immunoglobulin levels in relation to levels of specific antibodies in allogeneic and autologous bone marrow transplant recipients.

BACKGROUND: The aim of this study was to investigate the correlation of total levels of immunoglobulins to levels of specific antibodies after allogeneic and autologous bone marrow transplantation. Autologous transplant patients had normal levels of IgA and IgG antibodies already at 6 months after transplantation. In allogeneic transplanted patients without chronic graft versus host disease the immunological recovery was slower. The IgA and IgG levels were at the limit for deficiency at 6 months after transplantation. In allogeneic transplant patients with chronic chronic graft versus host disease the immunological recovery was delayed further. The total IgG levels were low at 12 months after transplantation and the IgG subclass pattern did not normalize until 24 months after transplantation. IgA levels remained low at 24 months after transplantation in all allogeneic transplanted patients with chronic chronic graft versus host disease. Protective levels of specific antibodies against tetanus and pneumococci decreased during the first year after transplantation regardless of the total immunoglobulin levels, regardless of the donors immunity. Pneumococcal antibodies decreased only in allogeneic transplanted patients, although autologous transplant patients retained pretransplant immunity against pneumococci. There was no difference in levels of specific antibodies between patients with and without chronic chronic graft versus host disease at 12 months after transplantation. There was no correlation between total immunoglobulin levels to levels of specific antibodies against tetanus and pneumococci after transplantation in our study. Taken together, normalized immunoglobulin levels do not predict normalization of levels of specific antibodies against tetanus and pneumococci after transplantation.

Stimulation of NK cell, T cell, and monocyte functions by the novel immunomodulator Linomide after autologous bone marrow transplantation. A pilot study in patients with acute myeloid leukemia.

Immunostimulatory therapy is at present considered after autologous bone marrow transplantation (ABMT) in order to mimic the allogeneic graft-versus-leukemia effect and thereby reduce the relapse rate. In a pilot study, five adults with acute myeloid leukemia were treated with the new immunomodulator Linomide post-ABMT. Linomide (0.3 mg/kg/week orally) was given in cycles of three weeks followed by three weeks of rest for up to six months. During treatment periods cyclic increases of CD56+CD3- and CD16+ NK cells were observed in parallel with enhanced cytotoxic activity of patient cells against both the NK-sensitive K562 and NK-resistant Daudi cell lines. A cyclic increase of CD14+ monocytic cells was also recorded. The proliferative responses of patient cells to PHA and allogeneic cells (MLC) were enhanced during Linomide therapy. The in vitro production of TNF alpha, IFN gamma, and IL-1 followed the same cyclic increase during treatment periods. Side effects were generally mild, and no harmful effects on engraftment were seen. Linomide therapy after ABMT thus induces a broad immunostimulation that offers a potential benefit with regard to leukemia-free survival.

B lymphocyte regeneration in marrow and blood after autologous bone marrow transplantation: increased numbers of B cells carrying activation and progression markers.

The reconstitution of B cells in the bone marrow and peripheral blood was prospectively studied in 27 patients undergoing autologous bone marrow transplantation (ABMT). No major differences in B cell regeneration patterns were recorded between patients receiving marrows purged of B cells (anti-CD10 + 19; n = 17) and patients receiving unpurged marrows (n = 10). Compared with healthy controls, elevated absolute and relative numbers of B cells were recorded in the blood and marrow at +6 and +12 months in both groups of patients. CD23+ B cells were severely depressed during the first three months post ABMT, indicating immaturity. A twofold increase in B cells carrying the activation marker 4F2 was recorded in the marrow at +1 month. Serum immunoglobulin levels (IgG, IgA, IgM) were within low-normal range throughout the study. The depressed B cell responses reported after allogeneic and autologous BMT could in part be explained by the low expression of the CD23 antigen on B cells after such therapy.

Successful pregnancy in a 28-year-old patient autografted for acute lymphoblastic leukemia following myeloablative treatment including total body irradiation.

We report a successful pregnancy in a woman who at the age of 28 years received total body irradiation (TBI; 7.5 Gy) and high-dose chemotherapy prior to autografting of purged bone marrow for acute lymphoblastic leukemia. Four years after transplantation she delivered a healthy girl. Only five previous cases of successful pregnancies are described in the literature after conditioning regimens including TBI. This case shows that restored ovarian function is possible after TBI in spite of prolonged exposure to chemotherapeutic agents during induction and consolidation therapy and relatively high age at the time of transplantation.

Subclinical disturbances in cardiac function at rest and in gas exchange during exercise are common findings after autologous bone marrow transplantation.

A study was undertaken to examine the effects of autologous bone marrow transplantation (BMT) on cardiac function at rest (n = 111) and pulmonary gas exchange during exercise (n = 110). Left ventricular cardiac ejection fraction (LVEF) was measured by radionuclide ventriculography before autologous BMT and after 6 months and 1, 3 and 5 years. Expired gas volume per oxygen consumption (VE/VO2) and transcutaneous PO2 were measured at rest and during submaximal exercise before and 6 and 12 months after autologous BMT, and the alveolar-arterial oxygen difference was calculated after 12 months. In lymphoma patients conditioned with BCNU, cyclophosphamide, etoposide and cytarabine, a long-lasting reduction in LVEF of 11 +/- 14% mean (+/- SD) was noted. The risk of cardiac deterioration was not increased by a subnormal LVEF before autologous BMT or total body irradiation (TBI). Impaired gas exchange during exercise was a common feature, but severe disturbances were uncommon. During exercise transcutaneous PO2 fell pathologically in 15% and 20% of the patients examined after 6 and 12 months, respectively, and the alveolar-arterial oxygen difference increased pathologically in 50% after 12 months. The VE/VO2 ratio increased significantly during exercise 6 months after autologous BMT in TBI-treated patients.

Impaired glucose tolerance after autologous bone marrow transplantation.

In this study we investigated glucose tolerance in relation to autologous bone marrow transplantation (ABMT). In 13 adult patients with acute myeloblastic (AML) or lymphoblastic (ALL) leukaemia in complete remission (CR), intravenous glucose tolerance test (IVGTT) was performed 1 month before and 6 months after ABMT. Patients with AML in CR received, as myeloablative therapy, cyclophosphamide combined with busulphan or total body irradiation (TBI). ALL patients received total body irradiation in combination with vincristine, daunorubicin, Ara-C, cyclophosphamide and prednisone. Before ABMT all patients, in spite of the intensive chemotherapy given for remission induction and consolidation, had a normal glucose tolerance. However, 6 months after the transplantation the k-value (rate of glucose elimination) for this group of patients had decreased (p less than 0.01). The trend towards impaired glucose tolerance was correlated with lower peak insulin values during IVGTT (p less than 0.05). Thus, the myeloablative therapy in connection with ABMT caused an impairment of pancreatic beta-cell function. No patient has hitherto developed clinical diabetes mellitus.

Pulmonary function and complications subsequent to autologous bone marrow transplantation.

Risk factors for early pulmonary complications occurring within the first 3 months after autologous bone marrow transplantation (BMT) were analysed in 158 consecutive adults. The long-term effects of autologous BMT on pulmonary function were analysed in 102 patients, who had survived free of disease for > 6 months after autologous BMT. Pulmonary function tests were performed before, at 6 and 12 months after autologous BMT and thereafter annually. The median follow-up was 12 (6-60) months. The incidence of early pulmonary complications was 16% (26 of 158). Idiopathic interstitial pneumonitis was seen in 11% of patients treated with total body irradiation (TBI). Single dose TBI was the major risk factor as regards early pulmonary complications but restrictive pulmonary disturbances and impaired diffusing capacity prior to autologous BMT were also significant risk factors. In both non-TBI and TBI-treated patients a mild restrictive ventilatory dysfunction and impaired diffusing capacity was noted 6 months after autologous BMT. In non-TBI-treated patients, these disturbances had resolved completely within 2 years whereas the lung volumes of TBI-treated patients were persistently reduced by 10% of their pre-autologous BMT values during follow-up. However, dysfunctions rarely progressed 6 months after autologous BMT. In most patients, ventilatory dysfunction was slight and had no clinical significance.

Haemolytic uraemic syndrome and renal dysfunction following BEAC (BCNU, etoposide, ara-C, cyclophosphamide) +/- TBI and autologous BMT for malignant lymphomas.

Twenty-four patients autografted for malignant lymphoma have been followed. All were conditioned with BEAC (BCNU, etoposide, ara-C, cyclophosphamide), in 10 patients combined with total body irradiation (TBI) 7.5 Gy. Within 1 month of ABMT, a capillary leak syndrome was seen in four patients (one death) and isolated pericarditis in one. Nineteen patients survive disease-free at > or = 6 months, median (range) 24 (11-48) months. In 15 of 19 patients, a decrease in glomerular filtration rate (GFR) of > 20% was observed, 6 (6-24) months after ABMT. In six of these patients (five treated with TBI), the renal dysfunction was still progressing 11-36 months after ABMT. Five patients (four conditioned with TBI) developed a haemolytic uraemic syndrome (HUS) with Coombs negative haemolytic anaemia, platelet consumption and renal impairment, with onset 3-6 months after ABMT. Haemolysis and platelet consumption, but not renal impairment, were reversible in all patients. One death from HUS was seen. Because of the adverse effects described we have abandoned the combination of BEAC with TBI.

Dose-dependent mobilisation of haematopoietic progenitor cells in healthy volunteers receiving glycosylated rHuG-CSF.

In an attempt to optimise the dose of G-CSF for mobilisation of PBPC in allogeneic donors, four groups of six healthy male volunteers received lenograstim (glycosylated rHuG-CSF) at a dose of 3, 5, 7.5 or 10 micrograms/kg/day, respectively, for 6 days (days 1-6). All subjects underwent a 10 I leukapheresis. Lenograstim was well tolerated. Maximal mobilisation was observed on days 5 or 6, with a clear dose-response for all progenitor cell types (CD34+, CFU-GM, BFU-E, CFU-mix). The peak numbers of CD34+ cells/microlitre (mean, s.e.m.) were 30 +/- 5, 49 +/- 8, 44 +/- 5 and 122 +/- 30 in the 3, 5, 7.5 and 10 micrograms/kg groups, respectively. A good correlation was observed between the number of CD34+ cells in blood and leukapheresis product (LP), respectively. Increasing the dose of lenograstim did not increase the number of T cells in the LP. A comparison of LP and steady state BM CD34+ cells in paired samples from each individual, showed a higher proportion of primitive immunophenotypes (CDw90+, HLA-DR-, CD45RA-, CD33-) among LP CD34+ cells. We conclude that increased doses of G-CSF improve the mobilisation of PBPC, and that G-CSF favours mobilisation of primitive CD34+ cell subsets. Lenograstim 10 micrograms/kg/day for 6 days should provide a sufficiently effective mobilisation of PBPC in most healthy PBPC donors.

Thyroid function after autologous bone marrow transplantation.

Thyroid function was prospectively analysed in 111 consecutive patients in relation to autologous bone marrow transplantation (ABMT). Median follow-up time was 12 (range 3-60) months. As part of the conditioning treatment 58 patients had received total body irradiation (TBI) as a single dose of 7.5 Gy (dose rate 0.15 Gy/min). Thyroxine, triiodothyronine, thyrotropin (TSH) and thyroid antibodies were analysed before ABMT, every third month during the first year afterwards and then once annually. Thyroid dysfunction was seen in 20 patients (after TBI in 16, after non-TBI treatments in four). Five of these, all treated with TBI, developed primary hypothyroidism and in 15 compensated hypothyrosis, transient in eight (40%), was seen. There was a highly significant (p less than 0.001) increase, within the normal range, in median TSH level, prior to ABMT compared with 1 year following ABMT. In patients who developed thyroid dysfunction, the TSH level before ABMT was significantly higher (p less than 0.001) than in those who remained euthyroid. In four patients persistent elevated thyroid antibody titers appeared and in two of them hypothyrosis developed. No correlation between thyroid dysfunction and age was noted. The findings are similar to those after allogeneic BMT described by others.